Immune response in mammals, including humans, is most predictably induced by parenteral (injectable) administration of a protein antigen. Oral administration of a protein antigen is usually an ineffective route of immunization. Indeed, oral administration of a protein may be immunosuppressive rather than immunogenic (Mowat, A. M. 1987, "The Regulation of Immune Responses to Dietary Protein Antigens," Immunol. Today, 8: 93). Thus, development of a method for efficient oral immunization would be extremely desirable. Immunization has beneficial therapeutic effects in many areas of clinical medicine. Specifically, antimicrobial vaccines consisting of bacteria, viruses and their products are beneficial in preventing and combating infections. Also, allergy immunotherapy, a treatment in which injections of small doses of allergens results in alleviation of allergy symptoms, is important in therapy of inhalant allergies, venom allergies and anaphylaxis. Finally, treatment of autoimmune diseases with autoantigens or their components can alleviate the autoimmune diseases, as discussed in PCT application W092/06708. Luciano Adorini, et al., Approaches Toward Peptide Based Immunotherapy of Autoimmune Diseases Springer Seminar in Immunopathology Immunoprotein (1992)14: 187-199. Further, rejection of transplanted organs can be reduced by injection of MHC Class I and Class II antigens. Mohamed H. Sayegh, et al., Induction of Immunity and Oral Tolerance With Polymorphic Class II Major Histocompatibility Complex in the Rat, Proc. Nat. Acad. Sc. USA (1992) 89 7762-7766.
Collectively, we refer to these proteins as therapeutic since they exert a therapeutic effect through activating the immune system of humans and mammals. These immunotherapeutic proteins are all susceptible to proteolytic enzymatic digestion and other denaturing and degrading processes such as acid pH digestion.
Immunization by oral administration of therapeutic proteins has been quite ineffective in the past. It is believed that these proteins are damaged or destroyed by gastric and intestinal juices, thus losing their immunogenicity by the time they reach the lymphoid (immune) tissue in the gastrointestinal tract.